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Direct exposure to Ultraviolet (UV) radiation causes progressive damages in retinal cells, which is one of the hypothetical mechanisms underlying age-related retinopathy or macular degeneration. The protective effects of Apocynin against UV damages were firstly tested in retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs). Subsequently the beneficial effect of Apocynin on mouse retinas against light damage were examined. Next, microarray profiling was used to identify the genes regulated by Apocynin in both RPEs and RGCs. A candidate gene was isolated for functional characterization by knock-down study. Apocynin was shown to inhibit cell death, reduce oxidative stress and deoxyribonucleic acid damages in both RPEs and RGCs challenged with UV. Intravitreal application of Apocynin also improved retinal dysfunction caused by light damage. Sirtuin 1 (SIRT1) was identified as induced by Apocynin by microarray study. The induction was confirmed by realtime-PCR and western blotting. Knocking down SIRT1 antagonized the protective effect of Apocynin against UV damages in both RPEs and RGCs. Apocynin is a novel agent that shows both in vitro and in vivo efficacies against UV radiation induced retina damages. SIRT1 pathway is implicated in UV radiation protection of Apocynin in retinal cells.

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Long non-coding RNAs (lncRNAs) are a class of RNAs with the length exceeding 200 base pairs (bps), which do not encode proteins, nevertheless, lncRNAs have many vital biological functions. A large number of novel transcripts were discovered as a result of the development of high-throughput sequencing technology. Under this circumstance, computational methods for lncRNA prediction are in great demand. In this paper, we consider global sequence features and propose a stacked ensemble learning-based method to predict lncRNAs from transcripts, abbreviated as PredLnc-GFStack. We extract the critical features from the candidate feature list using the genetic algorithm (GA) and then employ the stacked ensemble learning method to construct PredLnc-GFStack model. Computational experimental results show that PredLnc-GFStack outperforms several state-of-the-art methods for lncRNA prediction. Furthermore, PredLnc-GFStack demonstrates an outstanding ability for cross-species ncRNA prediction.

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BACKGROUND: The effects of exposing Apis mellifera larvae to common insecticides were tested in the laboratory. RESULTS: The acute toxicity values of the four insecticides that we tested ranged from high toxicity to low toxicity: deltamethrin > cypermethrin > carbaryl > acetamiprid. The NOAEC (no observed adverse effect concentration) values of the chronic toxicity tests for each compound are 5 mg/L for acetamiprid, 2 mg/L for carbaryl, 1 mg/L for cypermethrin, and 0.2 mg/L for deltamethrin. CONCLUSION: According to the risk quotient (RQ) values of acute and chronic toxicity that we obtained, the risk is acceptable at exposure rates that have been identified in the field. Overall, our results are valuable for evaluating the acute and chronic toxicities of these insecticides to developing honey bees. This article is protected by copyright. All rights reserved.

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A regioselective cis-hydroalkylation of internal alkynes with readily prepared Katritzky pyridinium salts for the synthesis of tri-substituted alkenes is described. This reaction is the first example of a metal-catalyzed hydroalkylation of an alkyne via C-N bond activation of an amine. The reaction demonstrates broad scope and functional group tolerance, allowing access to desired products with high diversity. Preliminary mechanistic studies indicate that a combination of an SET-initiated radical process and Ni-catalyzed alkylation could engage in the reaction, which makes it possible to bypass the traditional open-shell addition pathway.

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BACKGROUND: Elevated plasma total homocysteine level is a risk factor for various vascular diseases; however, an association with risk of thromboangiitis obliterans (TAO) has not been defined. This study aims to assess whether elevated plasma total homocysteine level is associated with risk of TAO. METHODS: We performed a matched case-control study including 64 patients with TAO and 256 controls. Multivariate logistic regression models were used to estimate the association between elevated plasma homocysteine level and the risk of TAO. Interaction and stratified analyses were conducted according to age, sex, smoking, alcohol consumption, and histories of chronic diseases. RESULTS: Patients with TAO vs. controls had a higher mean plasma total homocysteine level (21.2 ± 12.8 µmol/L vs. 14.1 ± 4.9 µmol/L, P15 µmol/L (95% CI, 1.2-11.7). 1 µmol/L increase in plasma total homocysteine level was associated with 20% higher risk of TAO (OR: 1.2; 95% CI, 1.1-1.3). CONCLUSION: Our findings suggest the risk of TAO was significantly associated with elevated plasma total homocysteine level independently of other factors analyzed, including smoking. Studies on the use of homocysteine-lowering therapy to prevent TAO would allow testing causality of the latter association.

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As we all know, microvalve holds great importance for microfluidic manipulation in chip. Herein, a simple method of high-performance multiplex microvalves chip fabrication was reported. In this method, a sandwich structure is established by inserting a polydimethylsiloxane (PDMS) membrane into two glasses, which is cheap and simple without any complex silicon-based device or soft lithography. Taking advantages of both the elasticity of the PDMS and the rigidity of glass, the microvalve chip showed good controls performance and had the ability of multiplex integration. Moreover, aided by a computer design program, this microvalves chip can be performed automatically, showing great potential to develop new highly integrated microfluidic devices. In addition, the fabricated multiplex microvalve chip is further successfully used for staining tumor cells automatically, improving the efficiency of cell identification process and reducing human errors. These results indicate this method opens up new avenues for multiplex microvalves fabrication and its biological application.

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Chinese herbal medicines used in combination have long-term been shown to be mild remedies with "integrated effects." However, our study provides the first demonstration that M1, an active metabolite of ginsenoside, exerted its dramatic therapeutic effects on accelerated and severe lupus nephritis (ASLN) mice, featuring acute renal function impairment, heavy proteinuria, high serum levels of anti-dsDNA, and high-grade, diffuse proliferative renal lesions. In the present study, NZB/WF1 mice were given injections of lipopolysaccharide to induce the ASLN model. M1 (30 mg/kg) was then administered to the mice by gavage daily, and the mice were sacrificed on week 3 and week 5 after the induction of disease. To identify the potential mechanism of action for the pure compound, levels of NLRP3 inflammasome activation in bone marrow-derived dendritic cells (BMDCs), podocytes and macrophages, and antigen-specific T cell activation in BMDCs were determined in addition to mechanistic experiments in vivo. Treatment with M1 dramatically improved renal function, albuminuria and renal lesions and reduced serum levels of anti-dsDNA in the ASLN mice. These beneficial effects with M1 treatment involved the following cellular and molecular mechanistic events: [1] inhibition of NLRP3 inflammasome associated with autophagy induction, [2] modulation of T help cell activation, and [3] induction of regulatory T cell differentiation. M1 improved the ASLN mice by blunting NLRP3 inflammasome activation and differentially regulating T cell functions, and the results support M1 as a new therapeutic candidate for LN patients with a status of abrupt transformation of lower-grade (mesangial) to higher-grade (diffuse proliferative) nephritis.

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Long noncoding RNAs are important regulators of gene expression in innate immune responses. Antisense IL-7 (IL-7-AS) is a newly discovered long noncoding RNA in human and mouse that has been reported to regulate the expression of IL-6. However, the potential function of IL-7-AS in innate immune system is not fully understood. In this study, we found that the expression of IL-7-AS is primarily dependent on the NF-κB and MAPK signaling pathways in macrophages and intestinal epithelial cells. Functionally, IL-7-AS promotes the expression of several inflammatory genes, including CCL2, CCL5, CCL7, and IL-6, in cells in response to LPS. Specifically, IL-7-AS physically interacts with p300 to regulate histone acetylation levels around the promoter regions of these gene loci. Moreover, IL-7-AS and p300 complex modulate the assembly of SWI/SNF complex to the promoters. IL-7-AS regulates chemotaxis activity of monocytes to intestine epithelial cells with involvement of CCL2. Therefore, our data indicate a new promoting role for NF-κB/MAPK-responsive IL-7-AS in the transcriptional regulation of inflammatory genes in the innate immune system although modulation of histone acetylation around the promoters of related genes.

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It is known that lethal viruses profoundly manipulate host metabolism, but how the metabolism alternation affects the immediate host antiviral immunity remains elusive. Here, we report that the O-GlcNAcylation of mitochondrial antiviral-signaling protein (MAVS), a key mediator of interferon signaling, is a critical regulation to activate the host innate immunity against RNA viruses. We show that O-GlcNAcylation depletion in myeloid cells renders the host more susceptible to virus infection both in vitro and in vivo. Mechanistically, we demonstrate that MAVS O-GlcNAcylation is required for virus-induced MAVS K63-linked ubiquitination, thereby facilitating IRF3 activation and IFNß production. We further demonstrate that D-glucosamine, a commonly used dietary supplement, effectively protects mice against a range of lethal RNA viruses, including human influenza virus. Our study highlights a critical role of O-GlcNAcylation in regulating host antiviral immunity and validates D-glucosamine as a potential therapeutic for virus infections.

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Iminoctadine tris (albesilate) is a bis-guazatine fungicide, and its specific modes of action and efficacy against C. cassiicola are not yet clear. In this study, baseline sensitivity data for mycelial growth showed that the frequency distribution curve of iminoctadine tris (albesilate) EC50 values is unimodal. The EC50 values ranged from 0.1151 to 1.2101â¯µg/mL, with a mean of 0.5775â¯±â¯0.2677â¯µg/mL. Iminoctadine tris (albesilate) affected the morphological development of C. cassiicola, causing increased branching of the mycelium. The significant increase in membrane permeability and malondialdehyde content after iminoctadine tris (albesilate) treatment indicated that this fungicide caused severe damage to the membrane structure. Furthermore, 0.4â¯µg/mL iminoctadine tris (albesilate) could decrease the spore density of C. cassiicola from 2.6200â¯×â¯104 to 1.4967â¯×â¯104/cm2 on average in vitro, indicating that the fungicide had great potential to reduce secondary infection with C. cassiicola in the field. Additionally, 120â¯µg/mL iminoctadine tris (albesilate) provided over 95% curative efficacy and 81.17% preventative efficacy on detached cucumber leaves inoculated with C. cassiicola. In field trials, iminoctadine tris (albesilate) at a dose of 120â¯g a.i./ha exhibited 72.92% and 80.92% control efficacy in 2017 and 2018, respectively. However, the efficacy supplied by the reference fungicide azoxystrobin at 250â¯g a.i./ha was only approximately 50% due to the development of fungicide resistance in C. cassiicola. Taken together, the findings above provide a solid foundation for the exploration of the action mechanisms of iminoctadine tris (albesilate) against C. cassiicola and provide overwhelming evidence for the use of iminoctadine tris (albesilate) as an excellent potential alternative fungicide in the management of cucumber Corynespora leaf spot.

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OBJECTIVE: This study aimed to investigate the relationship between obesity and pathologic features and biochemical recurrence in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP) after neoadjuvant hormonal therapy (NHT). METHODS: A total of 422 consecutive patients with clinically localized PCa who received NHT before RP were retrospectively analyzed. Unconditional multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) regarding probability. A receiver operating characteristic (ROC) curve was used to assess the efficacy of the predictive variables. Castration resistance free survival curves were obtained using the Kaplan-Meier method, and were compared using the log-rank test. RESULTS: Being overweight was associated with an increased risk of positive margins (OR 2.281; 95% CI 1.292-4.028) after adjusting for potential confounders. The area under the ROC curve for overweight patients was larger than that for patients in the normal weight range. There was no significant difference between the overweight and normal weight groups regarding castration resistance free survival. CONCLUSIONS: Being overweight was associated with positive margins in patients with PCa undergoing RP after NHT.

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BACKGROUND: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes. METHODS: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation. RESULTS: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of ß cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial. CONCLUSIONS: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and ß-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

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Neuroimaging studies have shown that the anterior cingulate cortex (ACC) is consistently activated by thirst and may underlie the affective motivation of drinking behaviour demanded by thirst. But direct evidence for this hypothesis is lacking. The present study evaluated potential correlations between ACC neuronal activity and drinking behaviour in rats injected with different concentrations of saline. We observed an increased number of c-Fos-positive neurons in the ACC after injection of hypertonic saline, indicating strong ACC neuronal activation under hyperosmotic thirst. Increased firing rates of putative ACC pyramidal neurons preceded drinking behaviour and positively correlated with both the total duration of drinking and the total amount of water consumed. Chemogenetic inhibition of ACC pyramidal neurons changed drinking behaviour from an explosive and short-lasting pattern to a gradual but more persistent pattern, without affecting either the total duration of drinking or the total amount of water consumed. Together, these findings support a role of the ACC in modulating the affective-motivative dimension of hyperosmolality-induced thirst.

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Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme-mediated 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) loaded ABTS@MIL-100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging-guided combined tumor therapy. The as-constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme-mediated "two-step rocket-launching-like" process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H2 O2 level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor-triggered PTT. More importantly, the H2 O2 -activated and acid-enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme-involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.

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Non-fullerene based organic solar cells (OSCs) have made a huge breakthrough in the recently years. Introducing proper side chain on the π-conjugated backbone plays a vital role for further improving power conversion efficiency (PCE) of OSCs due to easy tuning of the physical properties of the molecule such as absorption, energetic level, solid-state stacking and charge transporting. More importantly, the side chain significantly affected the blend film's morphology and thus determined the PCEs of the devices. In this work, two low bandgap non-fullerene acceptors (NFAs), ATT-4 and ATT-5, with alkyl or branched alkyl substitute on indacenodithiophene (IDT) and thieno[3,4-b]thiophene (TbT) backbone, were synthesized for investigating the substituent effects on the performance of the NFAs. In comparison to ATT-1 with p-hexylphenyl-substituted IDT and n-octyl-substituted TbT moieties, ATT-4 and ATT-5 exhibit better crystallinity with shorter interchain distances and ordered molecular structure in neat and the corresponding blend films. The tailored ATT-5 exhibits a high PCE of 12.36% with a Voc of 0.93 V, Jsc of 18.86 mA cm-2, and FF of 0.71 blending with wide bandgap polymer donor PBDB-T. Remarkably, though ATT-4 and ATT-5 exhibit broader light absorption, the devices obtained higher Voc than that of ATT-1 mainly due to the reduced non-radiative recombination in the blend films with increased electron mobility. These results implied that the side chain engineering is an efficient approach in regulating the electronic structure and molecular packing of NFAs, which can well match with polymer donor and obtain high PCEs of the OSCs with improved Voc, Jsc and FF, simultaneously.

RESUMO

Salinity is detrimental to plant growth, crop production and food security worldwide. Excess salt triggers increases in cytosolic Ca2+ concentration, which activate Ca2+-binding proteins and upregulate the Na+/H+ antiporter in order to remove Na+. Salt-induced increases in Ca2+ have long been thought to be involved in the detection of salt stress, but the molecular components of the sensing machinery remain unknown. Here, using Ca2+-imaging-based forward genetic screens, we isolated the Arabidopsis thaliana mutant monocation-induced [Ca2+]i increases 1 (moca1), and identified MOCA1 as a glucuronosyltransferase for glycosyl inositol phosphorylceramide (GIPC) sphingolipids in the plasma membrane. MOCA1 is required for salt-induced depolarization of the cell-surface potential, Ca2+ spikes and waves, Na+/H+ antiporter activation, and regulation of growth. Na+ binds to GIPCs to gate Ca2+ influx channels. This salt-sensing mechanism might imply that plasma-membrane lipids are involved in adaption to various environmental salt levels, and could be used to improve salt resistance in crops.

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Spin-orbit (SO) interaction is an indispensable element in the field of spintronics for effectively manipulating the spin of carriers. However, in crystalline solids, the momentum-dependent SO effective magnetic field generally results in spin randomization by a process known as the Dyakonov-Perel spin relaxation, leading to the loss of spin information. To overcome this obstacle, the persistent spin helix (PSH) state with a unidirectional SO field was proposed but difficult to achieve in real materials. Here, on the basis of first-principles calculations and tight-binding model analysis, we report for the first time a unidirectional SO field in monolayer transition metal dichalcogenides (TMDs, MX2, M = Mo, W; and X = S, Se) induced by two parallel chalcogen vacancy lines. By changing the relative positions of the two vacancy lines, the direction of the SO field can be tuned from x to y. Moreover, using k·p perturbation theory and group theory analysis, we demonstrate that the emerging unidirectional SO field is subject to both the structural symmetry and 1D nature of such defects engineered in 2D TMDs. In particular, through transport calculations, we confirm that the predicted SO states carry highly coherent spin current. Our findings shed new light on creating PSH states for high-performance spintronic devices.

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Synthetic microbial consortia are a rapidly growing area of synthetic biology. So far, most consortia are designed without considering their environments; however, in nature, microbial interactions are constantly modulated by cellular contexts, which, in principle, can dramatically alter community behaviors. Here we present the construction, validation, and characterization of an engineered bacterial predator-prey consortium that involves a chloramphenicol (CM)-mediated, context-dependent cellular interaction. We show that varying the CM level in the environment can induce success in the ecosystem with distinct patterns from predator dominance to prey-predator crossover to ecosystem collapse. A mathematical model successfully captures the essential dynamics of the experimentally observed patterns. We also illustrate that such a dependence enriches community dynamics under different initial conditions and further test the resistance of the consortium to invasion with engineered bacterial strains. This work exemplifies the role of the context dependence of microbial interactions in modulating ecosystem dynamics, underscoring the importance of including contexts into the design of engineered ecosystems for synthetic biology applications.

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